The mechanical properties of cartilage which permit the tissue to reversibly absorb load can be largely attributed to the quality, quantity and organization of collagen and proteoglycan in the extracellular matrix. However, it is the contribution of quantitatively minor components of cartilage, the chondrocytes, which permit the appropriate balance of these macromolecules in the matrix. The ability of these cells to respond to changes in their environment plays a central role assuring the presence of the appropriate macromolecules in the matrix. These cells are known to be able to alter their metabolism in response to the quantity or quality of loading forces. The mechanism by which the chondrocytes are capable of modulating their synthetic patterns in response to these physical changes is not known. In fact, when one considers the complexities of the forces to which these cells are exposed during an idealized loading cycle, it becomes apparent that we do not know which environmental factor, or combination of factors, is primarily responsible for the cellular response. There are at least three major elements of the load cycle to which the cells may respond: 1. Changes in hydrostatic pressure without deformation of either the cells or matrix, 2. Changes in the electrical environment from streaming potentials, giving rise to currents flowing past the cells, and 3. a physical deformation of the cells resulting in an alteration of cell shape. When cartilage tissue is deformed, all these factors are present at the same time, due to the amount and composition of the matrix, making the study of these factors on an individual basis difficult. We plan on circumventing such difficulties by using isolated cells for the experiments, to minimize the contribution of the extracellular matrix. It is therefore planned to examine how variations in the magnitude, frequency and exposure time with respect to different hydrostatic pressures, electrical currents and amounts of cellular deformation affect the rate of proteoglycan synthesis by chondrocytes. In addition, an analysis of the mechanical characteristics of isolated cells surrounded by different amounts of extracellular matrix will be performed. These studies should lead to a better understanding of the mechanisms by which chondrocytes respond to changes in their environment and to a better description of the mechanical properties of these cells in the presence and absence of the extracellular matrix.